Bone marrow mesenchymal stem cells derived from patients with ankylosing spondylitis show abnormal immunoregulation capability on macrophages

doi:10.3969/j.issn.2095-4344.2016.01.003

Abstract

Abstract:

BACKGROUND: Ankylosing spondylitis is an autoimmune disease at high inflammatory state, and its pathogenesis is still unclear. Besides, there is a lack of entirely satisfactory curative strategies.

OBJECTIVE: To explore the immunoregulation capability of bone marrow mesenchymal stem cells from ankylosing spondylitis patients on macrophages and the potential therapeutic use of bone marrow mesenchymal stem cells from healthy donors on ankylosing spondylitis.

METHODS: Bone marrow mesenchymal stem cells were extracted from 21 healthy donors and 25 ankylosing spondylitis patients respectively, and passage 4 cells were used in subsequent experiments. A human monocytic cell line was induced to differentiate into macrophages. The phenotypic markers of bone marrow mesenchymal stem cells and macrophages were detected by flow cytometry. Expressions of tumor necrosis factor-α and tumor necrosis factor-α-stimulated gene 6 (TSG-6) proteins in the supernatant of co-culture system were detected by ELISA. Quantitative real-time PCR was applied to detect the mRNA level of cytokines secreted by bone marrow mesenchymal stem cells and macrophages.

RESULTS AND CONCLUSION: The typical mesenchymal stem cell surface markers were expressed in both bone marrow mesenchymal stem cells from healthy donors and patients with ankylosing spondylitis, and CD68 was detected positively in induced macrophages. The protein and mRNA levels of tumor necrosis factor-α secreted by macrophages co-cultured with bone marrow mesenchymal stem cells from patients with ankylosing spondylitis were obviously higher than those from healthy donors (P < 0.05). TSG-6 secreted by bone marrow mesenchymal stem cells from patients with ankylosing spondylitis was lower than that by bone marrow mesenchymal stem cells from healthy donors in both RNA transcriptional and protein levels (P < 0.05). Our study demonstrates that bone marrow mesenchymal stem cells from patients with ankylosing spondylitis shows abnormal immunoregulatory function on inhibiting the tumor necrosis factor-α secretion from macrophages, which reveals a mechanism of immune disorder in ankylosing spondylitis. The therapeutic mechanism of bone marrow mesenchymal stem cells from healthy donors may work by secreting enough TSG-6 to inhibit the activation of macrophages in patients with ankylosing spondylitis, and thereby to decrease the secretion of tumor necrosis factor-α.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

CLC Number:

R394.2

Sun Su-he, Wang Peng, Su Chun-yan, Xie Zhong-yu, Li Yu-xi,Li Deng, Wang Shan, Su Hong-jun, Wu Xiao-hua, Deng Wen, Wu Yan-feng, Shen Hui-yong . Bone marrow mesenchymal stem cells derived from patients with ankylosing spondylitis show abnormal immunoregulation capability on macrophages[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(1): 13-19.

Figures/Tables 4

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